In this paper, the effects of the blend of nanoparticles and microneedle matrix materials on the mechanical properties of dissolving microneedles were studied mainly, so as to construct microneedles with excellent mechanical properties. Different kinds of nanoparticles (calcium carbonate, hydroxyapatite, silica), particle sizes (20, 60, 100 nm) and the proportion of prescription (2%, 6%, 10%) were blended with the matrix material [polyvinyl pyrrolidone (PVP), poly(1-vinylpyrrolidone-co-vinyl acetate)(PVP/VA)] to form dissolving microneedles. The effects of nanoparticles on the elastic modulus and hardness of the microneedles were investigated using a nanoindenter. The results showed that the elastic modulus and hardness of PVP microneedles were significantly improved by nano-calcium carbonate (P < 0.001), and the elastic modulus and hardness of PVP/VA microneedles were significantly improved by nano-hydroxyapatite (P < 0.001). When the particle size of hydroxyapatite was 20 nm, the elastic modulus of PVP/VA microneedles was (10.6 ± 1.0) GPa, and the hardness was (0.47 ± 0.06) GPa. As the size of the nanoparticles increases, the mechanical performance of the microneedles decreases. When the mass proportion of nano-hydroxyapatite increased from 2% to 6%, the elastic modulus and hardness of the microneedles were significantly improved (P < 0.001), but the effect of continue increasing the proportion of nanoparticles on the microneedles was not significant. The nano-enhanced PVP/VA dissolving microneedles has no irritant effect on intact skin and has a slight irritation to damaged skin, but they disappear completely after 72 h. Animal experiments have been approved by the Laboratory Animal Welfare and Ethics Committee of Zhejiang University of Technology. Therefore, the nano-enhanced dissolving microneedles has good biological safety. To sum up, it is necessary to select the appropriate kind of nanoparticle, particle size, and prescription ratio when microneedles constructing with a given matrix material, so as to effectively improve its mechanical performance.

The inflammatory reaction after acute cerebral infarction can aggravate the cerebral ischemic reperfusion injury.Activation of peroxisome proliferator-activated receptors-γ(PPAR-γ) has neuroprotective effects by which induces anti-inflammatory actions in cerebral ischaemia,thus as a potential novel pharmacological target for ischemic stroke was regarded.Acupuncture can improve cerebral ischemia injury by inhibiting synthesis of inflammatory cytokines,downregulating expressions of inflammatory mediators and adhesion molecule,suppressing the functions of inflammatory cells.Therefore,it will be a promising orientation to sift the effective acupuncture for that can stimulate the activation of PPAR-γ,and the research of mechanism of acupuncture on anti-inflammatory reaction after cerebral ischemic by activating PPAR-γ dependent pathways.

Beta-Elemene is an antitumor drug which is isolated from the traditional Chinese medicinal herb Curcumae Phaeocaulis Rhizoma, it is the main component of elemene which is extracted from the plant and delivered via blood circulation after intravenous injection. The antitumor effect of beta-elemene in vitro and in vivo was definite, and beta-elemene could improve the patient immunity and no sever side effect, drug resistance or bone marrow suppression were found during the clinical studies. And human serum albumin (HSA) is a primary extracellular protein which has a high concentration distribution in blood plasma and has many characteristic physiological functions. Therefore, the binding of beta-elemene to protein may be very important for absorption, distribution, metabolism and elimination. Therefore, the study on the interaction of beta-elemene with drug-carrying protein is very important. In this work, molecular binding of beta-elemene to human serum albumin (HSA) was investigated by using spectrofluorometer. the binding constants suggested that a strong interaction and the formation of a complex between beta-elemene and HSA. This clearly implies that beta-elemene can be stored and removed by the proteins in the body. Furthermore, the fluorescence quenching results showed that the HSA fluorescence was quenched by beta-elemene through static quenching mechanism. Thermodynamic parameters showed that hydrophobic interactions play a role in the binding of beta-elemene to HSA. The negative deltaH(0) and positive deltaS(0) in case of beta-elemene therefore showed that electrostatic attraction play a role in the binding of beta-elemene to HSA.
Drugs, Chinese Herbal ; chemistry ; Humans ; Kinetics ; Protein Binding ; Serum Albumin ; chemistry ; Sesquiterpenes ; chemistry ; Spectrometry, Fluorescence ; Thermodynamics

Objectives:To investigate the differentiation of human hepatocellular carcinoma cell line Bel-7404 induced by Matrine in vitro,and discuss its mechanism.Methods:After dealing human hepatocellular carcinoma cell line Bel-7404 with different concentrations of Matrine,we drew cell growth curve by MTT colorimetry,and cell morphology was examined by light microscope.Then we evaluated the tumor cell biological characteristics changes through improved soft agarose clone forming test,cell adhesion assay,cell movement assay and cell invasion assay.Also we detemined cell cycle distributing by flow cytometry.Results:After 72 hours being treated with 0.5,0.75,1.0g/L,in the Matrine test groups,the cell proliferation was inhibited significantly,and cell shape transformed to normal.The amounts of clone were remarkably reduced.The cell adhesion ability increased in different level.At the same time cell ability of movement and invasion differently weakened.Analysis of cell cycle shown that along with rising of Matrine concentration,the cell amounts in G1 phase increased accordingly and cell amounts in G2 and S phase remarkbly decreased.Conclusion:During the appropriate concentration range,Matrine not only inhibited Bel-7404 growth and proliferation,but also induced tumor cell to differentiate.Its probably mechanism may related to cell cycle regulation.

Objective:To investigate the door-to-balloon (D2B) time and its influencing factors for Percutaneous Coronary Intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods:180 cases of patients with STEMI in our hospital from January 2014 to April 2016 were selected.PCI therapy were operated on all patients after their consent.The pre-hospital delay time and D2B time of the patients were recorded.The related information of the patients,including demographic data,clinical factors,background of the disease and psychological factors,were investigated by the questionnaire survey.The patients were divided into short D2B group (D2B time≤ 126 min,n=96) and long D2B group (D2B time＞126 min,n=84).Univariate and multivariate logistic regression methods were used to analyze the influencing factors of D2B time.Results:The median D2B time of all the patients was 126 min,and only 26.7％ of patients' D2B time controlled within 90 min.Univariate analysis showed that differences of sudden attack,pay attention to symptoms,someone was present when attack,symptoms progress was fast,in hospital during holiday,no symptom in CCU,outpatient treatment,transfered by emergency medical service system (EMSS),time in CCU (6 am-10 pm),angina before infarction and pre-hospital delay time between the two groups were statistically significant (P＜0.05).Multivariate logistic regression analysis showed that in hospital during holiday,outpatient service,no symptom in CCU,pay attention to symptoms,use of transfered by EMSS,time in CCU (6am-10pm) are the factors affecting the time of D2B (OR=2.62,2.04,1.59,0.52,0.28,0.61 P＜0.05).Conclusion:The D2B time of most patients with STEMI can not reach the guidelines.The factors of patients,doctors,accepting mechanism of hospital are all related with D2B time.

Objective: To investigate the expression changes in transport receptor and catabolic enzymes of amyloid β-protein (Aβ) in the brain of aged rats after surgery.

Objective To investigate a new method and to observe the clinical effect of repairing the lower eyelid ectropion assisted with the subcutaneous pedicle flap from temporal region. Methods Since 2007, 24 patients with lower eyelid ectropion were treated with the subcutaneous pedicle flap from temporal region which was the donor area without hairs, including 8 cases of scar infection, 6 cases of trauma, and 10 cases of tumor removal. Among the 24 cases of the flap, the maximum area was 5. 5 cm× 1. 5 cm,and the minimum was 4. 0 cm × 1.0 cm. Results All patients were followed up for 6 months to 3 years.All flaps survived completely with excellent texture and appearance. The donor site was hidden and no obvious malformation of the donor site was observed. Conclusions Because the blood supply of flap is reliable and the incision in the donor site is hidden, the subcutaneous pedicle flap from temporal region pedicled with arterial network of the outer canthus is an ideal donor site for repairing the lower eyelid ectropion with full thickness defects.

To investigate the influence factors and effects of metal or dissolving microneedles on the formation and healing of skin microchannels, the pencil-shaped or conical stainless steel microneedles with different lengths, tip to tip space and base area, and the pencil-shaped dissolving microneedles with different tip to tip space were used. The microneedles were applied to the skin of epilatory mice and rats, and the effects of various microneedle parameters, application parameters, and animals on the microchannels were explored by the transepidermal water loss (TEWL) and methylene blue staining. Visually observe the skin local irritation caused by the microneedles. The animal experiments were approved by the Animal Experiments Welfare and Ethical Committee of Zhejiang University of Technology. The application time of the microneedle should be maintained at 30 s or more. When the insertion forces were 2, 4, 8 N, and the TEWL initial values of the formed microchannels were 12.9, 33.0, 40.4 g·m^-2·h^-1, respectively. When the length of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 37.1, 40.4, 49.5 g·m^-2·h^-1, respectively. When the tip to tip space of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 33.2, 40.4, 55.8 g·m^-2·h^-1, respectively. When the base area of metal microneedle were 0.16, 0.35, 0.62 cm², and the TEWL initial values of the formed microchannels were 35.1, 40.4, 67.1 g·m^-2·h^-1, respectively. The effects of conical and pencil-shaped microneedles are similar. When the tip to tip space of pencil shaped dissolving microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 49.8, 60.5, 70.5 g·m^-2·h^-1, respectively. The TEWL baseline values of animal skins of different genders and series are different, but the tendency of microchannels formation and closure is similar. Visual inspection revealed that the slight erythema caused by the microneedles subsided within 24 h. Microneedles of different parameters have different effects on microchannels. The microchannels closed within 24 or 48 h, and the skin local irritation caused by microneedle was mild.

This study examined the osteogenic effect of electromagnetic fields (EMF) under the simulated in vivo conditions. Rat bone marrow mesenchymal stem cells (BMSCs) and rat osteoblasts were co-cultured and exposed to 50 Hz, 1.0 mT EMF for different terms. Unexposed single-cultured BMSCs and osteoblasts were set as controls. Cell proliferation features of single-cultured BMSCs and osteoblasts were studied by using a cell counting kit (CCK-8). For the co-culture system, cells in each group were randomly chosen for alkaline phosphatase (ALP) staining on the day 7. When EMF exposure lasted for 14 days, dishes in each group were randomly chosen for total RNA extraction and von Kossa staining. The mRNA expression of osteogenic markers was detected by using real-time PCR. Our study showed that short-term EMF exposure (2 h/day) could obviously promote proliferation of BMSCs and osteoblasts, while long-term EMF (8 h/day) could promote osteogenic differentiation significantly under co-cultured conditions. Under EMF exposure, osteogenesis-related mRNA expression changed obviously in co-cultured and single-cultured cells. It was noteworthy that most osteogenic indices in osteoblasts were increased markedly after co-culture except Bmp2, which was increased gradually when cells were exposed to EMF. Compared to other indices, the expression of Bmp2 in BMSCs was increased sharply in both single-cultured and co-cultured groups when they were exposed to EMF. The mRNA expression of Bmp2 in BMSCs was approximately four times higher in 8-h EMF group than that in the unexposed group. Our results suggest that Bmp2-mediated cellular interaction induced by EMF exposure might play an important role in the osteogenic differentiation of BMSCs.

Objective To report our surgical experience in treating 19 cases of solitary iliac aneurysms (SIA). Methods The clinical data of 19 consecutive patients with SIA between January 1985 and January 2008 were retrospectively reviewed. There were 18 men and 1 woman, aging from 39 to 77 years ( mean 62 ± 7 years). Results There were 30 SIAs in the 19 patients, including 25 ( 83.3% ) common iliac aneurysms, 4 (13.3%) internal ihac aneurysms and 1 (3. 3% ) external iliac aneurysm. Eleven patients ( 57.9% ) had multiple ancurysms, with 9 patients ( 47.4% ) having bilateral SIA. Two patients had coexistent peripheral vascular occlusive disease. There were 2 patients suffering form ruptured SIA, one was saved by emergency operation and one died before an surgery could be attempted. Seventeen patients underwent successful open aneurysmectomy and artificial graft implantation leaving no ischemic complications of the pelvic organs. One patient with right common iliac aneurysm underwent endovascular repair without endoleak. There was no operative death during porioperative period. The surviving patients remained stable and had good patency of grafts during the follow-up period. Conclusions Early management of SIA is important, CT angiogarphy (CTA) is necessary not only to evaluate the SIAs, but also to detect multiple aneurysms or arterial occlusive disease. Close and long-term follow-up is mandatory for the early detection of the formation of new anearysms.